Abstract
The safety and precision of peptide antigens has prompted the search for adjuvants capable of increasing the immune response against these intrinsically poorly immunogenic antigens. The integration of both immunostimulants and peptide antigens within nanometric delivery systems for their co-delivery to immune cells is a promising vaccination strategy. With this in mind, the potential synergistic effect of the immunostimulant poly (I:C) (pIC) and a T-Helper peptide (PADRE), integrated into a chitosan (CS) based nanostructure, was explored. The value of this nanostructured combination of materials was assessed for a peptide antigen (1338aa) derived from the HPV-16 L2 protein. These nanoparticles, produced by ionic gelation technique, exhibited a nanometric size (<300 nm), a high positive surface charge (>40 mV) and high pIC association efficiency (>96%). They also showed capacity for the association of both the 1338aa and PADRE peptides. The influence of the presence of pIC and PADRE in the nanocomposition, as well as that of the peptide presentation form (encapsulated versus surface adsorbed) on the antibody induction was evaluated in a preliminary in vivo study. The data obtained highlights the possibility to engineer nanoparticles through the rational combination of a number of adjuvant molecules together with the antigen.
Highlights
The advent of synthetic peptide-based antigens has brought new opportunities and new challenges to the development of effective vaccines
With this idea in mind, three main components were chosen for the formation of the nanostructures: chitosan, known for its capacity to facilitate antigen presentation to the immune system when presented in a nanometric structure [6,7], poly (I:C), a potent immunostimulant, and a T-Helper peptide (PADRE)
We report for the first time, a chitosan nanostructure designed to co-deliver a Toll-like receptor 3 (TLR3) agonist (Poly (I:C)) and a T-helper peptide (PADRE) as adjuvant system for a HPV-derived peptide antigen
Summary
The advent of synthetic peptide-based antigens has brought new opportunities and new challenges to the development of effective vaccines. From the technological point of view, they are easy to produce under appropriate quality control practices [1] and present little risk of contamination by pathogenic or toxic substances [2] Due to their purity, these entities lack “danger signals” [3] and are incapable of activating immune cells. There is a need to design adjuvant systems adapted to facilitate the efficient presentation of peptide-based antigens without compromising their favorable safety profile. Within this context, nanoparticles made of biodegradable polymers are receiving increasing attention
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